Abstract
Background
Atezolizumab plus bevacizumab has recently been approved as a new first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC).
Objective
We performed a real-world study to evaluate the impact of the IMbrave150 trial inclusion criteria on the safety and efficacy of treatment outside of clinical trials.
Methods
We analyzed patients treated with atezolizumab plus bevacizumab for unresectable HCC from four different countries. No specific inclusion and exclusion criteria were applied, except for the absence of previous systemic therapies for HCC. The entire population was split into two groups according to concordance with the inclusion criteria as reported in the IMbrave150 trial in ‘IMbrave150-in’ and ‘IMbrave150-out’ patients, and safety and efficacy in the two groups of patients were evaluated.
Results
Overall, 766 patients were included in the analysis: 561/766 (73%) in the ‘IMbrave150-in’ group and 205/766 (27%) in the ‘IMbrave150-out’ group. Median overall survival (OS) and median progression-free survival (PFS) were 16.3 versus 14.3 months (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.35–0.65; p < 0.0001] and 8.3 versus 6.0 months (HR 0.79, 95% CI 0.63–0.99; p = 0.0431) in ‘IMbrave150-in’ and ‘IMbrave150-out’ patients, respectively. Multivariate analysis confirmed that patients included in the ‘IMbrave150-in’ group had significantly longer OS compared with patients included in the ‘IMbrave150-out’ group (HR 0.76, 95% CI 0.47–0.97; p = 0.0195). In ‘IMbrave150-in’ patients, the albumin-bilirubin (ALBI) grade was not associated with OS, whereas in ‘IMbrave150-out’ patients, those with ALBI grade 1 reported a significant benefit in terms of OS compared with those with ALBI grade 2 (16.7 vs. 5.9 months; HR 4.40, 95% CI 2.40–8.08; p > 0.0001). No statistically significant differences were reported in the ‘IMbrave150-in’ and ‘IMbrave150-out’ groups in terms of safety profile.
Conclusion
Adherence to the IMbrave150 trial inclusion criteria favorably impacts the prognosis of patients receiving atezolizumab plus bevacizumab. Among patients who did not meet the IMbrave150 inclusion criteria, those with ALBI grade 1 could benefit from the treatment.
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Conflicts of interest
Lorenza Rimassa reports receiving consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Servier, Taiho Oncology, and Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi, and Servier; travel expenses from AstraZeneca; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, and Zymeworks. Tiziana Pressiani has received consulting fees from Bayer, Ipsen, and IQVIA, and institutional research funding from Bayer, Lilly, and Roche. Fabian Finkelmeier has received travel support from Ipsen, and speaker’s fees from AbbVie, MSD, Ipsen, Eisai, and Fresenius. Mario Scartozzi has received grants and personal fees from MERCK, MSD, Servier, Eisai, and Amgen. Andrea Casadei-Gardini has received grants and personal fees from MSD, Eisai, and Bayer, and is an advisor for MSD, Eisai, Bayer, Bristol-Myers Squibb, AstraZeneca, and GSK. Margherita Rimini, Mara Persano , Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Ho Yeong Lim, José Presa, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Fabio Piscaglia, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Valentina Burgio, and Stefano Cascinu declare they have no conflicts of interest that might be relevant to the contents of this manuscript.
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The Ethical Review Board of each Institutional Hospital approved the present study. This study was performed in line with the principles of the Declaration of Helsinki.
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Written informed consent for treatment was obtained for all patients.
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Authors' contributions
Conception and design: ACG, MR. Acquisition of data (acquired and managed patients): All authors. Analysis and interpretation of data: ACG, MR. Writing, review, and/or revision of the manuscript: ACG, MR. Final approval of the manuscript: All authors.
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Rimini, M., Persano, M., Tada, T. et al. Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis?. Targ Oncol 18, 221–233 (2023). https://doi.org/10.1007/s11523-023-00953-x
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DOI: https://doi.org/10.1007/s11523-023-00953-x